Probing of Triply Coordinated Oxygen in Amorphous Al₂O₃

Although anomalous melt properties have been attributed to the presence of triply coordinated oxygen (^[3]O), the presence of ^[3]O in covalent amorphous oxides has not been revealed experimentally; such verification is the Holy Grail in the study of the physics and chemistry of glasses. We report the first ¹⁷O NMR spectrum for amorphous Al₂O₃ and reveal the hidden nature of ^[3]O. The detailed NMR characteristics of the oxygen tricluster are distinct from those estimated for the crystalline analogs, thus indicating its unique structure. This unambiguous evidence of the presence of ^[3]O allows us to microscopically constrain its glass-forming ability and unique two-step crystallization paths of amorphous Al₂O₃ through the annihilation of glassy ^[3]O with multiple ^[5]Al species

HnRNP Q suppresses polyglutamine aggregation by reducing Vaccinia-related kinase 2 mRNA stability

Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which encodes a polyglutamine tract in the HTT protein. Misfolding of proteins containing abnormal expansions of polyglutamine (polyQ) repeats is associated with cytotoxicity in HD. We have previously shown that vaccinia-related kinase 2 (VRK2) downregulates chaperonin TRiC protein levels through the ubiquitin-proteasome system by recruiting the E3 ligase COP1 and by destabilizing USP25 which is deubiquiting enzyme. Here we found that basal level of VRK2 in neuronal cells is regulated by post-transcriptional regulation. HnRNP Q specifically binds to 3’UTR of VRK2 mRNA in neuronal cells and reduces its stability. We report a dramatic increase polyglutamine aggregation by reducing hnRNP Q level. Thus, our results demonstrate that decreased brain hnRNP Q contributes to HD neurological phenotype and open new novel prognostic marker of HD.1

Synergistic Composite Coating for Separators in Lithium Metal Batteries

Despite their conspicuous advantages in energy density, lithium metal batteries (LMBs) are still in the research stage owing to uncontrolled lithium dendrite growth, which deteriorates their cycle life and safety. In this study, we aim to formulate a separator coating and identify the optimal coating conditions that are scalable with the ultimate goal of fabricating separators that largely address the chronic issues of LMBs. For this purpose, a mixture of an ionic liquid, a block copolymer, and microspheres was applied to a conventional polyethylene separator. While the polymeric microspheres mechanically strengthen the coating layer against lithium dendrite growth, the ionic liquid and block copolymer support lithium ion conduction and provide robust connections among the composite components, all jointly resulting in a uniform lithium ion flux, which in turn results in plated lithium metal with a highly compact morphology. Alongside improved thermal stability, this composite coating enables superior cyclability in Li parallel to Li symmetric and Li parallel to Cu asymmetric cells as well as pouch-type full cells. The simple, scalable nature of the present coating approach renders it useful not only for lithium metal batteries currently in development but also for common commercial lithium ion batteries, which suffer from severe lithium plating upon fast charging.

HnRNPQ suppresses polyglutamineaggregation by post-transcriptional regulation of vaccinia-related kinase 2

Themisfoldingofproteinswithabnormallypolyglutamine(polyQ)expansioncauseneurodegenerativedisordersincludingHuntington'sdisease(HD).TCP-1ringcomplex(TRiC)/Chaperonin-containing TCP-1(CCT)hasanessentialroleinprotectingagainsttheaggregationandcytotoxicityofpolyQproteins.Notably,wehavepreviouslyshownthatvaccinia-relatedkinase2(VRK2)downregulateschaperoninTRiCproteinlevelsthroughtheubiquitin-proteasomesystembydestabilizingubiquitin-specificprotease25(USP25). VRK2expressionisknowntobemuchhigherinactivelyproliferatingcells,butismaintainedatalowlevelinthebrainbecauseitmakescellspronetopolyQaggregation.Herewefoundthatneuronalcell-specificbasallevelofVRK2isregulatednotbytranscriptionalregulationbutbypost-transcriptionalregulation. HnRNPQspecificallybindsto3’UTRofVrk2mRNAinneuronalcellsandreduceditsmRNAstability.WereportadramaticdecreaseinCCT4levelbyreducinghnRNPQ,whichcontributetoincreaseinpolyQaggregation.Thus,ourresultsdemonstratethatthelevelofbrainhnRNPQcontributestoHDprogressionbyregulatingVrk2mRNAstabilityandopennewnobleprognosticmarkerofHD.2

c-Abl Regulates the Pathological Deposition of TDP-43 via Tyrosine 43 Phosphorylation

Non-receptor tyrosine kinase, c-Abl plays a role in the pathogenesis of several neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Here, we found that TDP-43, which was one of the main proteins comprising pathological deposits in amyotrophic lateral sclerosis (ALS), is a novel substrate for c-Abl. The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells. The kinase-dead mutant of c-Abl had no effect on the cytoplasmic localization of TDP-43. The expression of phosphor-mimetic mutant Y43E of TDP-43 in primary cortical neurons accumulated the neurite granule. Furthermore, the phosphorylation of TDP-43 at tyrosine 43 by c-Abl promoted the aggregation of TDP-43 and increased neuronal cell death in primary cortical neurons, but not in c-Abl–deficient primary cortical neurons. Identification of c-Abl as the kinase of TDP43 provides new insight into the pathogenesis of ALS

Dendrite-Free Lithium Deposition for Lithium Metal Anodes with Interconnected Microsphere Protection

A lithium (Li) metal anode is required to achieve a high-energy-density battery, but because of an undesirable growth of Li dendrites, it still has safety and cyclability issues. In this study, we have developed a microsphere-protected (MSP) Li metal anode to suppress the growth of Li dendrites. Microspheres could guide Li ions to selective areas and pressurize dendrites during their growth. Interconnections between microspheres improved the pressurization. By using an MSP Li metal anode in a 200 mAh pouch-type Li/NCA full cell at 4.2 V, dendrite-free Li deposits with a density of 0.4 g/cm³, which is 3 times greater than that in the case of bare Li metal, were obtained after charging at 2.9 mAh/cm². The MSP Li metal enhanced the cyclability to 190 cycles with a criterion of 90% capacity retention of the initial discharge capacity at a current density of 1.45 mA/cm²